Role of Matrix Metalloproteinases in Blood Flow–Induced Arterial Enlargement

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Abstract
—Tears in the internal elastic lamina (IEL) can be observed after chronic increases in arterial blood flow, suggesting a potential role for matrix metalloproteinases (MMPs) in flow-induced vascular remodeling. We undertook to study this phenomenon by constructing an arteriovenous fistula (AVF) between the left common carotid artery (CCA) and the external jugular vein in rabbits. The diameter of the flow-loaded left CCA increased by 13.6±1.8% by day 3 after construction of the AVF compared with the right CCA (n=4, PPNG-nitro-l-arginine methyl ester to inhibit nitric oxide synthesis. MMP activities were significantly decreased in the left CCAs of NG-nitro-l-arginine methyl ester–treated animals. Hence, blood flow–induced MMP activation is critical in flow-induced vascular enlargement and IEL fragmentation, and blood flow–induced nitric oxide participates in MMP activation.